Riboflavin Phosphate Sodium Salt, also known as Riboflavin 5′-Phosphate Sodium or Riboflavin Sodium Phosphate, is a water-soluble phosphorylated form of vitamin B2 used as an active pharmaceutical ingredient and nutritional ingredient. It is particularly useful where a more water-soluble form of riboflavin is required.
The current BP/Ph. Eur. monograph identifies Riboflavin Sodium Phosphate as a semi-synthetic product derived from phosphorylation of riboflavin and describes it as Vitamin B2. The principal component is riboflavin 5′-(sodium hydrogen phosphate), accompanied by smaller amounts of other riboflavin monophosphates and diphosphates.
Riboflavin Phosphate Sodium Salt
The FDA Substance Registration System identifies Riboflavin 5′-Phosphate Sodium Dihydrate as an ingredient substance and lists 6184-17-4 among its identifiers. USP identifies the dihydrate as C₁₇H₂₀N₄NaO₉P·2H₂O with molecular weight 514.36.
Riboflavin Phosphate Sodium is the sodium salt of riboflavin 5′-monophosphate. Pharmacopoeial material recognizes that the substance contains the principal 5′-phosphate together with minor amounts of riboflavin, 3′-phosphate, 4′-phosphate and several diphosphate species.
The BP/Ph. Eur. specification requires 73.0–79.0% riboflavin on the dried-substance basis. This is important: the API should not be described as a conventional 98–102% single-component assay because the pharmacopoeial assay is expressed as the equivalent content of riboflavin.
The substance occurs as a yellow or orange-yellow, crystalline, hygroscopic powder. It is soluble in water and very slightly soluble in ethanol (96%).
Riboflavin Phosphate Sodium API is used in:
The Ph. Eur. monograph specifically lists Vitamins B and C Injection as a preparation in which Riboflavin Sodium Phosphate is used.
Riboflavin is vitamin B2 and acts as a precursor of the biologically active flavin coenzymes flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD).
FMN and FAD participate in numerous oxidation-reduction reactions involved in cellular energy metabolism. They are required for enzymes involved in carbohydrate, lipid and amino-acid metabolism and contribute to normal cellular function.
Riboflavin Phosphate Sodium therefore provides a phosphorylated, water-soluble source of vitamin B2 for pharmaceutical and nutritional applications.
Current BP/Ph. Eur. 11.6 material provides unusually detailed quality requirements for this API. The major controls include:
The current BP/Ph. Eur. related-substances procedure uses LC with detection at 266 nm and controls specified impurities F, G and H, unspecified impurities and total impurities.
Riboflavin Phosphate Sodium is produced through controlled phosphorylation of riboflavin followed by sodium salt formation, purification, concentration and drying.
A pharmaceutical-grade process should control:
Because the pharmacopoeial substance is defined as a mixture of related phosphate species, composition control is particularly important for this API.
These values are supported by the BP 2025 / Ph. Eur. 11.6 monograph.
Riboflavin Sodium Phosphate is hygroscopic and sensitive to light, particularly in solution. The current BP/Ph. Eur. monograph specifies storage in an airtight container, protected from light.
Suitable API packaging should therefore provide:
The FCC description also notes that the dry material is relatively stable under diffused light but that deterioration occurs rapidly when it is in solution and exposed to light.
Typical documentation available for Riboflavin Phosphate Sodium API may include:
A reliable Riboflavin Phosphate Sodium Salt API manufacturer should maintain tight control over phosphorylation chemistry, phosphate-isomer composition, moisture, related substances and assay.
The API should be manufactured according to an appropriate pharmaceutical quality system with validated analytical procedures and controlled packaging. Particular attention should be given to the 73.0–79.0% dried-basis riboflavin content, pH 5.0–6.5, specific rotation, related substances, inorganic phosphate and loss on drying specified by the pharmacopoeial standard.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 8.0% |
| pH (1% Solution) | 5.0 – 6.5 |
| Individual Impurity | NMT 0.7% |
| Total Impurities | NMT 2.0% |
| Water Content | NMT 2.0% |
| Specific Rotation | +38.0° to +43.0° (dried substance) |